Department of Anatomy and Cell Biology, University of Florida, Gainesville, Florida 32610, USA.
J Biol Chem. 2009 Dec 11;284(50):34901-10. doi: 10.1074/jbc.M109.038356. Epub 2009 Oct 11.
HDAC1 and -2 are highly conserved enzymes and often coexist in the same coregulator complexes. Understanding the regulation of histone deacetylase activities is extremely important because these enzymes play key roles in epigenetic regulation in normal and cancer cells. We previously showed that HDAC1 is required for glucocorticoid receptor-mediated transcription activation and that its activity is regulated through acetylation by p300 during the induction cycle. Here, we showed that HDAC2 is also required for glucocorticoid receptor-mediated gene activation. HDAC2, however, is regulated through a different mechanism from that of HDAC1. HDAC2 is not acetylated by p300, although 5 of 6 acetylated lysine residues in HDAC1 are also present in HDAC2. More importantly, the activity of HDAC2 is inhibited by acetylated HDAC1. Additionally, we showed that acetylated HDAC1 can trans-regulate HDAC2 through heterodimerization. Thus, this study uncovered fundamental differences between HDAC1 and HDAC2. It also unveiled a new mechanism of collaborative regulation by HDAC1/2 containing coregulator complexes.
HDAC1 和 -2 是高度保守的酶，通常存在于同一核心调节复合物中。了解组蛋白去乙酰化酶活性的调节非常重要，因为这些酶在正常和癌细胞的表观遗传调控中发挥关键作用。我们之前表明，HDAC1 是糖皮质激素受体介导的转录激活所必需的，其活性通过 p300 在诱导周期中的乙酰化来调节。在这里，我们表明 HDAC2 也需要糖皮质激素受体介导的基因激活。然而，HDAC2 的调节机制与 HDAC1 不同。虽然 HDAC1 中有 6 个乙酰化赖氨酸中的 5 个也存在于 HDAC2 中，但 HDAC2 不受 p300 的乙酰化。更重要的是，乙酰化的 HDAC1 可以抑制 HDAC2 的活性。此外，我们还表明，乙酰化的 HDAC1 可以通过异二聚化来调节 HDAC2。因此，这项研究揭示了 HDAC1 和 HDAC2 之间的根本差异。它还揭示了 HDAC1/2 包含的核心调节复合物的协同调节的新机制。
